Action Points

Older patients with nonmelanoma skin cancer showed less risk of developing Alzheimer's disease than those without nonmelanoma skin cancer.

Note that no significant association was found between non-melanoma skin cancer and subsequent development of all-cause dementia.

Older patients with nonmelanoma skin cancer showed less risk of developing Alzheimer's disease than those without such tumors, researchers reported.

In a longitudinal study involving more than 1,000 New York City residents older than 70, those with a history of nonmelanoma skin cancer had only one-fifth the likelihood of receiving an uncomplicated Alzheimer's disease diagnosis than those without these cancers (HR 0.21, 95% CI 0.051-0.87, P=0.031), according to Richard B. Lipton, MD, of Albert Einstein College of Medicine in New York City, and colleagues.

"We deduce Alzheimer-specific neuroprotection, because the effect is attenuated or eliminated when considering less-specific diagnoses such as Alzheimer's disease with another diagnosis ... or all-cause dementia," the researchers wrote online in Neurology.

Nor was the link associated with the less common but more aggressive melanoma, they stated.

Lipton and colleagues suggested that the cancer itself may have neuroprotective biological effects, perhaps involving DNA methylation, although they acknowledged the possibility that the results reflected confounding effects of other factors.

In particular, education could be such a confounder, the researchers indicated, because it is linked to healthier lifestyles and regular health examinations. Healthier lifestyles often include physical activity, which is protective against cognitive decline and dementia, they stated. In turn, outdoor physical activity offered greater exposure to ultraviolet radiation, which increases skin cancer risk.

"I find this intriguing, but we need to be careful," said Mathew M. Avram, MD, of Massachusetts General Hospital in Boston, who was not involved with the study.

"I think the take-home message for physicians out there is how important sun exposure is for development of skin cancers. And to the extent there is less sun exposure, you're going to have fewer of them," Avram said. "But the clinical implications we need to be careful of. It's not as if we are going to look at the study and change the way we advise our patients to avoid the sun and be careful in terms of sun protection and surveillance for skin cancers."

The findings emerged from the epidemiologic Einstein Aging Study (EAS), in which 1,102 older adults in the Bronx (mean age 79 at enrollment) with no baseline symptoms of dementia were followed for a median of 3.0 years (mean 3.7 years).

At the study's onset, 109 participants reported past incidence of nonmelanoma skin cancer. During follow-up, 32 people developed nonmelanoma skin cancer and 126 people developed dementia. One hundred among the 126 had Alzheimer's dementia.

Data in the primary analysis were adjusted for demographic variables, hypertension, diabetes, and coronary heart disease. When APOE epsilon-4 allele status was included as well, the point estimate was changed only slightly but the association was no longer statistically significant (HR 0.18, 95% CI 0.024-1.34, P=0.094).

Previous studies have observed an inverse relationship between Alzheimer's disease and cancer, Lipton and colleagues wrote. In African Americans with cancer, an increased AD risk was reported, but in whites, a previous cancer diagnosis conferred a reduced risk of Alzheimer's. There was no significant association between a previous diagnosis of cancer and future vascular dementia.

Lipton and colleagues stated that the study limitations, beyond the obvious difficulties with self-reported data, included not specifically asking about nonmelanoma skin cancer when the cancer data was collected. Also, diagnosis date for skin cancer was subject to recall bias, and APOE genotype data was not available for all participants.

The study was funded by the National Institute on Aging and the National Cancer Institute.